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Pharmacology, Toxicology and Environmental Health

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2011

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Full-Text Articles in Life Sciences

Degradation Of Atrazine By White Rot And Soil Fungi, Gerald Presley Dec 2011

Degradation Of Atrazine By White Rot And Soil Fungi, Gerald Presley

Undergraduate Honors Theses

The widespread use of atrazine in agriculture has lead to an abundance of this toxic chemical in the environment. Fungi that have the ability to degrade atrazine into less toxic products have been identified and used in the remediation of atrazine. In this study atrazine degradation in a defined liquid media was characterized in a diverse group of white rot basidiomycete and deuteromycete soil fungi. Atrazine did not have an effect on fungal growth although each species produced a different amount of biomass in culture. Statistical analysis showed that biomass production was an important factor in determining the amount of …


Minimal Structural Requirements Of Alkyl Γ-Lactones Capable Of Antagonizing The Cocaine-Induced Motility Decrease In Planarians, Debra Baker, Sean Deats, Peter Boor, James Pruitt, Oné R. Pagán Nov 2011

Minimal Structural Requirements Of Alkyl Γ-Lactones Capable Of Antagonizing The Cocaine-Induced Motility Decrease In Planarians, Debra Baker, Sean Deats, Peter Boor, James Pruitt, Oné R. Pagán

Biology Faculty Publications

We recently reported that the natural cyclic lactone, parthenolide, and related analogs prevent the expression of behavioral effects induced by cocaine in planarians and that parthenolide’s γ-lactone ring is required for this effect. In the present work, we tested a series of alkyl γ-lactones with varying chain length (1–8 carbons) to determine their ability to antagonize the planarian motility decrease induced by 200 μM cocaine. Alkyl lactones with up to a 4-carbon alkyl chain did not affect planarian motility or antagonized the cocaine-induced motility decrease; only the compound γ-nonalactone (a γ-lactone with a 5-carbon chain) was able to prevent the …


Reversal Of Glial And Neurovascular Markers Of Unhealthy Brain Aging By Exercise In Middle-Aged Female Mice, Caitlin S. Latimer, James L. Searcy, Michael T. Bridges, Lawrence D. Brewer, Jelena Popović, Eric M. Blalock, Philip W. Landfield, Olivier Thibault, Nada M. Porter Oct 2011

Reversal Of Glial And Neurovascular Markers Of Unhealthy Brain Aging By Exercise In Middle-Aged Female Mice, Caitlin S. Latimer, James L. Searcy, Michael T. Bridges, Lawrence D. Brewer, Jelena Popović, Eric M. Blalock, Philip W. Landfield, Olivier Thibault, Nada M. Porter

Pharmacology and Nutritional Sciences Faculty Publications

Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for …


Toxic Effects And Bioaccumulation Of Nano-, Micron- And Ionic-Ag In The Polychaete, Nereis Diversicolor, Yi Cong, Gary T. Banta, Henriette Selck, Deborah Berhanu, Eugenia Valsami-Jones, Valery E. Forbes Oct 2011

Toxic Effects And Bioaccumulation Of Nano-, Micron- And Ionic-Ag In The Polychaete, Nereis Diversicolor, Yi Cong, Gary T. Banta, Henriette Selck, Deborah Berhanu, Eugenia Valsami-Jones, Valery E. Forbes

Valery Forbes Publications

There is increasing concern about the toxicities and potential risks, both still poorly understood, of silver nanoparticles for the aquatic environment after their eventual release via wastewater discharges. In this study, the toxicities of sediment associated nano (<100 >nm)-, micron (2–3.5 μm)- and ionic (AgNO3)-Ag on the sediment-dwelling polychaete, Nereis diversicolor, were compared after 10 days of sediment exposure, using survival, DNA damage (comet assay) and bioaccumulation as endpoints. The nominal concentrations used in all exposure scenarios were 0, 1, 5, 10, 25, and 50 μg Ag/g dry weight (dw) sediment. Our results showed that Ag was able to cause …


Physiologically-Based Pharmacokinetic Modeling For Predicting Drug-Drug Interactions, David M. Ng, Ali Navid Aug 2011

Physiologically-Based Pharmacokinetic Modeling For Predicting Drug-Drug Interactions, David M. Ng, Ali Navid

STAR Program Research Presentations

Dynamics of interactions between the drugs caffeine and ciprofloxacin are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drugs are distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Multiple drugs can interact to increase or decrease their beneficial and/or undesired effects. This is important because some common substances, such as caffeine in coffee and soft drinks, are actually drugs that affect the body. By implementing the model as a computer program, it is relatively straightforward to perform …


Sr-A Ligand And M-Csf Dynamically Regulate Sr-A Expression And Function In Primary Macrophages Via P38 Mapk Activation, Dejan Nikolic, Lindsay Calderon, Liqin Du, Steven R. Post Jul 2011

Sr-A Ligand And M-Csf Dynamically Regulate Sr-A Expression And Function In Primary Macrophages Via P38 Mapk Activation, Dejan Nikolic, Lindsay Calderon, Liqin Du, Steven R. Post

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Inflammation is characterized by dynamic changes in the expression of cytokines, such as M-CSF, and modifications of lipids and proteins that result in the formation of ligands for Class A Scavenger Receptors (SR-A). These changes are associated with altered SR-A expression in macrophages; however, the intracellular signal pathways involved and the extent to which SR-A ligands regulate SR-A expression are not well defined. To address these questions, SR-A expression and function were examined in resident mouse peritoneal macrophages incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL).

RESULTS: M-CSF increased SR-A expression and function, and required the specific …


Importance Of Characterizing Nanoparticles Before Conducting Toxicity Tests, Yi Cong, Chengfang Pang, Lina Dai, Gary T. Banta, Henriette Selck, Valery E. Forbes Jul 2011

Importance Of Characterizing Nanoparticles Before Conducting Toxicity Tests, Yi Cong, Chengfang Pang, Lina Dai, Gary T. Banta, Henriette Selck, Valery E. Forbes

Valery Forbes Publications

Rapidly expanding growth in the field of nanotechnology has led to the development of numerous applications of nanomaterials in industrial (e.g., paints, electronics) and consumer (e.g., cosmetics, clothing treatments) products. These engineered nanoparticle (NP)-containing products have, however, the potential to release particles (single or aggregates) or ions by means of wastewater discharge into the aquatic environment. SCENIHR (2006) emphasized that the behavior of NPs is critically dependent on several particle characteristics, including size, surface area and surface reactivity, and that risk assessments for both human health and the environment have to be based on these characteristics. However, in practice, risks …


Formulation And Characterization Of Lipid-Based Drug Delivery System Of Raloxifene-Microemulsion And Self-Microemulsifying Drug Delivery System, Hetal Thakkar, Jitesh Nangesh, Mayur Parmar, Divyakant Patel Jul 2011

Formulation And Characterization Of Lipid-Based Drug Delivery System Of Raloxifene-Microemulsion And Self-Microemulsifying Drug Delivery System, Hetal Thakkar, Jitesh Nangesh, Mayur Parmar, Divyakant Patel

HPD Articles

BACKGROUND: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. MATERIALS AND METHODS: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. RESULTS: The results indicated that high …


Sp688 Radon In Tennessee, Courtney Nlemann, Martha Keel Jun 2011

Sp688 Radon In Tennessee, Courtney Nlemann, Martha Keel

Environment (Indoor & Outdoor)

Version 2.0


Archaeoparasitology Of Chaco Canyon, Rachel Paseka May 2011

Archaeoparasitology Of Chaco Canyon, Rachel Paseka

Department of Environmental Studies: Undergraduate Student Theses

Ancient cultures of the Colorado Plateau have been a focus of archaeoparasitology since its inception, and a vast parasitological history is recorded in coprolites preserved in this arid region. The inhabitants of Chaco Canyon dominated Ancestral Puebloan culture between 1050 and 1120 AD and were responsible for the construction of great towns, road systems, and early agriculture. Analysis of the parasites preserved in fecal remains contributes to an increased knowledge of ancient Chacoan health and culture. Nineteen coprolites from four sites in Chaco Canyon were rehydrated and analyzed microscopically for parasite remains. Rhabditiform and filariform nematode larvae were found from …


Assessing The Stability, Biological Transfer And Developmental Impact Of Environmentally Relevant Nitrosamines Using A Chicken Egg Model, Nikita Joshi May 2011

Assessing The Stability, Biological Transfer And Developmental Impact Of Environmentally Relevant Nitrosamines Using A Chicken Egg Model, Nikita Joshi

Toxicology Program: Dissertations, Theses, and Student Research

Nitrosamines comprise a large group of potentially toxic compounds occurring in the environment as by-products of various manufacturing, agricultural and natural processes. Nitrosamines are produced from reaction of nitrite with a suitable secondary amine in an acidic matrix; these acidic conditions can occur in environmental media and in the mammalian gastrointestinal (GI) tract. This research focused on the stability, transfer, and impacts of the environmentally relevant nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosmorpholine (NMOR), and N-nitrosoatrazine (NNAT) (formed from reaction of nitrite with dimethylamine, morpholine, and atrazine), using the chicken egg and embryo model systems. Chicken eggs were used to …


An Exploration Of Pharmacognosy And Its Potential In The Multi-Faceted Solution Required To Address Hiv/Aids In Sub-Saharan Africa, Alexandra Sassi Apr 2011

An Exploration Of Pharmacognosy And Its Potential In The Multi-Faceted Solution Required To Address Hiv/Aids In Sub-Saharan Africa, Alexandra Sassi

Pell Scholars and Senior Theses

This work has both both biological and anthropoligcal foci. It addresses research done on the medicinal properties of plants and how this research could make positive contributions to the current social and biological issues surrounding the HIV/AIDS epidemic in sub-Saharan Africa.


Deep Sleep And Parietal Cortex Gene Expression Changes Are Related To Cognitive Deficits With Age, Heather M. Buechel, Jelena Popovic, James L. Searcy, Nada M. Porter, Olivier Thibault, Eric M. Blalock Apr 2011

Deep Sleep And Parietal Cortex Gene Expression Changes Are Related To Cognitive Deficits With Age, Heather M. Buechel, Jelena Popovic, James L. Searcy, Nada M. Porter, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging.

METHODOLOGY: We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken.

PRINCIPAL FINDINGS: Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the …


Comparison Of Subcellular Responses For The Evaluation And Prediction Of The Chemotherapeutic Response To Cisplatin In Lung Adenocarcinoma Using Raman Spectroscopy, Haq Nawaz, Franck Bonnier, Aidan Meade, Fiona Lyng, Hugh Byrne Apr 2011

Comparison Of Subcellular Responses For The Evaluation And Prediction Of The Chemotherapeutic Response To Cisplatin In Lung Adenocarcinoma Using Raman Spectroscopy, Haq Nawaz, Franck Bonnier, Aidan Meade, Fiona Lyng, Hugh Byrne

Articles

Confocal Raman Micro spectroscopy (CRM) is employed to examine the chemical and physiological effects of anticancer agents, using cisplatin and A549 adenocarcinoma cells as a model compound and test system respectively. Spectral responses of the membrane and cytoplasm of the cell are analysed independently and the results are compared to previously reported spectroscopic studies of the nucleus. Moreover, Raman spectra from the proteins extracted from the control and exposed samples are acquired and analysed to confirm the origin of the molecular changes of the cell membrane and cytoplasm of the A549 cells. Multivariate data analysis techniques including Principal Component Analysis …


Library Impact Statement For Bps 455 Protein Molecular Modeling, Michael Vocino Mar 2011

Library Impact Statement For Bps 455 Protein Molecular Modeling, Michael Vocino

Library Impact Statements

Library Impact Statement for BPS 455 Protein Molecular Modeling. No new resources were required to support this course.


Le Développement Durable Comme Mode De Prévention Des Risques Energétiques : Une Approche Par Les Capacités D’Absorption. Le Cas De La Voiture Electrique Chez Renault, Sylvaine Castellano, Adnane Maâlaoui, Judith Schrempf-Stirling Mar 2011

Le Développement Durable Comme Mode De Prévention Des Risques Energétiques : Une Approche Par Les Capacités D’Absorption. Le Cas De La Voiture Electrique Chez Renault, Sylvaine Castellano, Adnane Maâlaoui, Judith Schrempf-Stirling

Management Faculty Publications

Sustainability — a way to prevent energy-related risks — is the buzzword of the last decade. This trend demands radical rethinking on how society lives, consumes and produces. Herein, we focus on electric cars, which is the result of sustainable processes and initiatives in the car industry. The case of Renault illustrates how the firm based its sustainable strategy on its absorptive capacities.


Parthenolide Blocks Cocaine’S Effect On Spontaneous Firing Activity Of Dopaminergic Neurons In The Ventral Tegmental Area, David Schwarz, Damaris Bloom, Rocío Castro, Oné R. Pagán, C. A. Jiménez-Rivera Mar 2011

Parthenolide Blocks Cocaine’S Effect On Spontaneous Firing Activity Of Dopaminergic Neurons In The Ventral Tegmental Area, David Schwarz, Damaris Bloom, Rocío Castro, Oné R. Pagán, C. A. Jiménez-Rivera

Biology Faculty Publications

Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaine’s locomotion effects in a planarian animal model (Pagán et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration …


Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry Jan 2011

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …


A Multidisciplinary Approach To Food Safety Evaluation: Hummus Spoilage And Microbial Analysis Of Kitchen Surfaces In Residential Child Care Institutions (Rcci) In Massachusetts, U.S.A., Elsina E. Hagan Jan 2011

A Multidisciplinary Approach To Food Safety Evaluation: Hummus Spoilage And Microbial Analysis Of Kitchen Surfaces In Residential Child Care Institutions (Rcci) In Massachusetts, U.S.A., Elsina E. Hagan

Masters Theses 1911 - February 2014

Food borne illnesses continues to be a public health challenge in the United States (U.S.); an estimated 9.4 million incident cases occurred in 2011. In view of this challenge we conducted two food safety studies; 1) related to product formulation (hummus spoilage challenge study) and 2) evaluating the microbial safety of domestic kitchen surfaces in Residential Child Care Institutions (RCCI pilot study).

Hummus is of Mediterranean origin but is currently eaten globally. This challenge study evaluates a variety of industrial hummus formulations (four in total, differing in pH and/or addition of a preservative (natamycin). Two batches were setup: batch 1; …


An Overview Of New Psychoactive Substances And The Outlets Supplying Them, Cathy Kelleher, Rachel Christie, Kevin Lalor, John Fox, Matt Bowden, Cora O'Donnell Jan 2011

An Overview Of New Psychoactive Substances And The Outlets Supplying Them, Cathy Kelleher, Rachel Christie, Kevin Lalor, John Fox, Matt Bowden, Cora O'Donnell

Reports

This report represents the outcome of a review of new psychoactive substances2 within the Irish context, including a review of the outlets that supply these substances. The review was commissioned by the National Advisory Committee on Drugs (NACD) in accordance with Action 14 of the National Drugs Strategy (interim) 2009–2016. Action 14 provides for the monitoring of ‘head shops’3 and other outlets for the sale of psychoactive substances, under the Misuse of Drugs Act 1977 and the Misuse of Drugs (Amendment) Regulations 2007. Researchers at the Centre for Social and Educational Research (CSER) within the School of Social Sciences and …


National Center For Pharmaceutical Crops, Wei Yuan, Shiyou Li, Zushang Su, Ping Wang Jan 2011

National Center For Pharmaceutical Crops, Wei Yuan, Shiyou Li, Zushang Su, Ping Wang

NCPC Presentations

The mission of the National Center for Pharmaceutical Crops is to develop crops for the production of pharmaceutical and other bioactive compounds. The NCPC, located in the Arthur Temple College of Forestry and Agriculture, is the only one of its kind in the U.S. and it seeks to improve human health, revitalize rural economies and enhance U.S. security in strategic pharmaceuticals. This poster provides a background to the department, its functions and activities and notable achievements.


Evaluating The Effectiveness Of A Commercial Portable Air Purifier In Homes With Wood Burning Stoves: A Preliminary Study, Julie Hart, Tony Ward, Terry Spear, Richard Rossi, Ph.D., Nicolas Holland M, Brodie Loushin Jan 2011

Evaluating The Effectiveness Of A Commercial Portable Air Purifier In Homes With Wood Burning Stoves: A Preliminary Study, Julie Hart, Tony Ward, Terry Spear, Richard Rossi, Ph.D., Nicolas Holland M, Brodie Loushin

Safety Health & Industrial Hygiene

Wood burning for residential heating is prevalent in the Rocky Mountain regions of the United States. Studies have shown that wood stoves can be a significant source of PM2.5 within homes. In this study, the effectiveness of an electrostatic filter portable air purifier was evaluated (1) in a home where a wood stove was the sole heat source and (2) in a home where a wood stove was used as a supplemental heat source. Particle count concentrations in six particle sizes and particle mass concentrations in two particle sizes were measured for ten 12-hour purifier on and ten purifier off …


Adding Value To Ecological Risk Assessment With Population Modeling, Valery E. Forbes, Peter Calow, Volker Grimm, Takehiko I, Hayashi, Tjalling Jager, Agnete Katholm, Annemette Palmqvist, Rob Pastorok, Dan Salvito, Richard Sibly, Julann Spromberg, John Stark, Richard A. Stillman Jan 2011

Adding Value To Ecological Risk Assessment With Population Modeling, Valery E. Forbes, Peter Calow, Volker Grimm, Takehiko I, Hayashi, Tjalling Jager, Agnete Katholm, Annemette Palmqvist, Rob Pastorok, Dan Salvito, Richard Sibly, Julann Spromberg, John Stark, Richard A. Stillman

Valery Forbes Publications

Current measures used to estimate the risks of toxic chemicals are not relevant to the goals of the environmental protection process, and thus ecological risk assessment (ERA) is not used as extensively as it should be as a basis for cost-effective management of environmental resources. Appropriate population models can provide a powerful basis for expressing ecological risks that better inform the environmental management process and thus that are more likely to be used by managers. Here we provide at least five reasons why population modeling should play an important role in bridging the gap between what we measure and what …


Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller Jan 2011

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …


Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan Jan 2011

Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan

Articles

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC50 values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …


Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2011

Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the …


Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2011

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC50 value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …


Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi Jan 2011

Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi

Department for Educational Development

No abstract provided.


Anaplasmataceae As Human Pathogens : Biology, Ecology And Epidemiology, Marina E. Eremeeva, Gregory A. Dasch Jan 2011

Anaplasmataceae As Human Pathogens : Biology, Ecology And Epidemiology, Marina E. Eremeeva, Gregory A. Dasch

Environmental Health Sciences Faculty Publications

This review describes the biology, ecology, and epidemiology of known human pathogens in the family Anaplasmataceae that are transmitted by ticks and belong to the genus Anaplasma and genus Ehrlichia. We discuss the current status of diagnosis and surveillance of the diseases they cause, and address the challenges and new perspectives raised due to continuous recognition of new emerging human pathogens in the family Anaplasmataceae.